1,6-Interactions between dimethylamino and aldehyde groups in two biphenyl derivatives

The title compounds, 2-(dimethylamino)biphenyl-2'-carboxaldehyde, C15H15NO, and 2-(dimethylamino)biphenyl-2',6'-dicarboxaldehyde, C16H15NO2, show similar 1,6-interactions [N...C=O 2.929 (3) to 3.029 (3) Å] between the dimethylamino and aldehyde groups located in the ortho positions of the two rings, which lie at 58.1 (1)-62.4 (1)° to each other

Glucagon-Like Peptide-1 Modulates Neurally-Evoked Mucosal Chloride Secretion in Guinea Pig Small Intestine In Vitro.

Glucagon-like peptide-1 (GLP-1) acts at the G protein-coupled receptor, GLP-1R, to stimulate secretion of insulin and to inhibit secretion of glucagon and gastric acid. Involvement in mucosal secretory physiology has received negligible attention. We aimed to study involvement of GLP-1 in mucosal chloride secretion in the small intestine. Ussing chamber methods, in concert with transmural electrical field stimulation (EFS), were used to study actions on neurogenic chloride secretion. ELISA was used to study GLP-1R effects on neural release of acetylcholine (ACh). Intramural localization of GLP-1R was assessed with immunohistochemistry. Application of GLP-1 to serosal or mucosal sides of flat-sheet preparations in Ussing chambers did not change baseline short-circuit current (Isc), which served as a marker for chloride secretion. Transmural EFS evoked neurally mediated biphasic increases in Isc that had an initial spike-like rising phase followed by a sustained plateau-like phase. Blockade of the EFS-evoked responses by tetrodotoxin indicated that the responses were neurally mediated. Application of GLP-1 reduced the EFS-evoked biphasic responses in a concentration-dependent manner. The GLP-1 receptor antagonist exendin-(9 –39) suppressed this action of GLP-1. The GLP-1 inhibitory action on EFS-evoked responses persisted in the presence of nicotinic or vasoactive intestinal peptide receptor antagonists but not in the presence of a muscarinic receptor antagonist. GLP-1 significantly reduced EFS-evoked ACh release. In the submucosal plexus, GLP-1R immunoreactivity (IR) was expressed by choline acetyltransferase- IR neurons, neuropeptide Y-IR neurons, somatostatin-IR neurons, and vasoactive intestinal peptide-IR neurons. Our results suggest that GLP-1R is expressed in guinea pig submucosal neurons and that its activation leads to a decrease in neurally evoked chloride secretion by suppressing release of ACh at neuroepithelial junctions in the enteric neural networks that control secretomotor functions

Glucagon-like peptide-2 modulates neurally evoked mucosal chloride secretion in guinea pig small intestine in vitro

Glucagon-like peptide-2 (GLP-2) is an important neuroendocrine peptide in intestinal physiology. It influences digestion, absorption, epithelial growth, motility, and blood flow. We studied involvement of GLP-2 in intestinal mucosal secretory behavior. Submucosal-mucosal preparations from guinea pig ileum were mounted in Ussing chambers for measurement of shortcircuit current (Isc) as a surrogate for chloride secretion. GLP-2 action on neuronal release of acetylcholine was determined with ELISA. Enteric neuronal expression of the GLP-2 receptor (GLP-2R) was studied with immunohistochemical methods. Application of GLP-2 (0.1–100 nM) to the serosal or mucosal side of the preparations evoked no change in baseline Isc and did not alter transepithelial ionic conductance. Transmural electrical field stimulation (EFS) evoked characteristic biphasic increases in Isc, with an initially rapid rising phase followed by a sustained phase. Application of GLP-2 reduced the EFS-evoked biphasic responses in a concentration-dependent manner. The GLP-2R antagonist GLP-2-(3-33) significantly reversed suppression of the EFS-evoked responses by GLP-2. Tetrodotoxin, scopolamine, and hexamethonium, but not vasoactive intestinal peptide type 1 receptor (VPAC1) antagonist abolished or reduced to near zero the EFS-evoked responses. GLP-2 suppressed EFS-evoked acetylcholine release as measured by ELISA. Pretreatment with GLP-2- (3-33) offset this action of GLP-2. In the submucosal plexus, GLP-2R immunoreactivity (-IR) was expressed in choline acetyltransferase-IR neurons, somatostatin-IR neurons, neuropeptide Y-IR neurons, and vasoactive intestinal peptide-IR neurons. We conclude that submucosal neurons in the guinea pig ileum express GLP-2R. Activation of GLP-2R decreases neuronally evoked epithelial chloride secretion by suppressing acetylcholine release from secretomotor neurons

Evidence that substance P does not mediate slow synaptic excitation within the myenteric plexus

ELECTRICAL stimulation of presynaptic fibres to the so-called AH1 or type II2 myenteric neurones in guinea pig small intestine evokes a slow excitatory postsynaptic potential (e.p.s.p.) characterised by long-lasting depolarisation associated with increased membrane resistance and augmented excitability3. Two substances have been implicated as possible neurotrans-mitters for the slow e.p.s.p. Katayama and North reported that application of substance P to myenteric neurones mimicked the slow e.p.s.p.4, and J.D.W. and C.J.M. presented several lines of evidence for serotonin as the transmitter substance5,6. We now report that methysergide, a drug which abolishes both the slow e.p.s.p. and the action of exogenous serotonin5,6, does not affect the action of substance P on guinea pig myenteric neurones. The results suggest that substance P is unlikely to be the neuro-transmitter which mediates the slow e.p.s.p

Developed single-phase turbulent flow through a square-pitch rod cluster for an extended range of reynolds numbers.

The mean velocity profiles wall shear stress distribution and all components of the Reynolds stress tensor have been determined from measurements for developed single-phase flow through a square-pitch rod cluster. For a rod pitch-to-diameter ratio of 1.107 four Reynolds numbers in the range 22.6 x 103 to 207.6 x 103 were investigated. The experimental technique which involved a rotatable inclined hot-wire anemometer probe allowed the measurement of secondary flow components of the order of 1 per cent of the local velocity. No evidence was found for secondary flows in the open rod gap area. The highly anisotropic nature of the turbulence particularly for the interconnecting rod gap region was shown by the level of the azimuthal turbulent shear stress. The mean velocity profiles were generally consistent with the logarithmic region of the universal velocity profile using the Patel values for the profile constants. The wall shear stress distribution measured by Preston tubes was shown to be symmetrical around the central rods of the array

Data bank of developed single-phase flow through a square-pitch rod cluster for four reynolds numbers.

Complete tabulated data of the mean velocity profiles wall shear stress distribution and all components of the Reynolds stresses are presented for developed single-phase flow through a square-pitch rod array (p/d = 1.107) at Reynolds numbers of 22.6 x 10 346.3 x 103 and 207.6 x 103

Gamma-Ray Telescopes (in "400 Years of Astronomical Telescopes")

The last half-century has seen dramatic developments in gamma-ray telescopes, from their initial conception and development through to their blossoming into full maturity as a potent research tool in astronomy. Gamma-ray telescopes are leading research in diverse areas such as gamma-ray bursts, blazars, Galactic transients, and the Galactic distribution of aluminum-26.Comment: 11 pages, 6 figures/ in "400 Years of Astronomical Telescopes: A Review of History, Science and Technology", ed. B.R. Brandl, R. Stuik, & J.K. Katgert-Merkeli (Exp. Astron. 26, 111-122 [2009]

A novel pathway producing dimethylsulphide in bacteria is widespread in soil environments

The volatile compound dimethylsulphide (DMS) is important in climate regulation, the sulphur cycle and signalling to higher organisms. Microbial catabolism of the marine osmolyte dimethylsulphoniopropionate (DMSP) is thought to be the major biological process generating DMS. Here we report the discovery and characterisation of the first gene for DMSP-independent DMS production in any bacterium. This gene, mddA, encodes a methyltransferase that methylates methanethiol (MeSH) and generates DMS. MddA functions in many taxonomically diverse bacteria including sediment-dwelling pseudomonads, nitrogen-fixing bradyrhizobia and cyanobacteria, and mycobacteria, including the pathogen Mycobacterium tuberculosis. The mddA gene is present in metagenomes from varied environments, being particularly abundant in soil environments, where it is predicted to occur in up to 76% of bacteria. This novel pathway may significantly contribute to global DMS emissions, especially in terrestrial environments, and could represent a shift from the notion that DMSP is the only significant precursor of DMS

Computer-based diabetes self-management interventions for adults with type 2 diabetes mellitus

BACKGROUND: Diabetes is one of the commonest chronic medical conditions, affecting around 347 million adults worldwide. Structured patient education programmes reduce the risk of diabetes-related complications four-fold. Internet-based self-management programmes have been shown to be effective for a number of long-term conditions, but it is unclear what are the essential or effective components of such programmes. If computer-based self-management interventions improve outcomes in type 2 diabetes, they could potentially provide a cost-effective option for reducing the burdens placed on patients and healthcare systems by this long-term condition. OBJECTIVES: To assess the effects on health status and health-related quality of life of computer-based diabetes self-management interventions for adults with type 2 diabetes mellitus. SEARCH METHODS: We searched six electronic bibliographic databases for published articles and conference proceedings and three online databases for theses (all up to November 2011). Reference lists of relevant reports and reviews were also screened. SELECTION CRITERIA: Randomised controlled trials of computer-based self-management interventions for adults with type 2 diabetes, i.e. computer-based software applications that respond to user input and aim to generate tailored content to improve one or more self-management domains through feedback, tailored advice, reinforcement and rewards, patient decision support, goal setting or reminders. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the abstracts and extracted data. A taxonomy for behaviour change techniques was used to describe the active ingredients of the intervention. MAIN RESULTS: We identified 16 randomised controlled trials with 3578 participants that fitted our inclusion criteria. These studies included a wide spectrum of interventions covering clinic-based brief interventions, Internet-based interventions that could be used from home and mobile phone-based interventions. The mean age of participants was between 46 to 67 years old and mean time since diagnosis was 6 to 13 years. The duration of the interventions varied between 1 to 12 months. There were three reported deaths out of 3578 participants.Computer-based diabetes self-management interventions currently have limited effectiveness. They appear to have small benefits on glycaemic control (pooled effect on glycosylated haemoglobin A1c (HbA1c): -2.3 mmol/mol or -0.2% (95% confidence interval (CI) -0.4 to -0.1; P = 0.009; 2637 participants; 11 trials). The effect size on HbA1c was larger in the mobile phone subgroup (subgroup analysis: mean difference in HbA1c -5.5 mmol/mol or -0.5% (95% CI -0.7 to -0.3); P < 0.00001; 280 participants; three trials). Current interventions do not show adequate evidence for improving depression, health-related quality of life or weight. Four (out of 10) interventions showed beneficial effects on lipid profile.One participant withdrew because of anxiety but there were no other documented adverse effects. Two studies provided limited cost-effectiveness data - with one study suggesting costs per patient of less than $140 (in 1997) or 105 EURO and another study showed no change in health behaviour and resource utilisation. AUTHORS' CONCLUSIONS: Computer-based diabetes self-management interventions to manage type 2 diabetes appear to have a small beneficial effect on blood glucose control and the effect was larger in the mobile phone subgroup. There is no evidence to show benefits in other biological outcomes or any cognitive, behavioural or emotional outcomes